سيلوكينزوك 50 مجم 28 قرص

12.1 Mechanism of Action Metoprolol is a beta 1 -selective (cardioselective) adrenergic receptor blocking agent. This preferential effect is not absolute, however, and at higher plasma concentrations, metoprolol also inhibits beta 2 -adrenoreceptors, chiefly located in the bronchial and vascular musculature. Metoprolol has no intrinsic sympathomimetic activity, and membrane-stabilizing activity is detectable only at plasma concentrations much greater than required for beta-blockade. Animal and human experiments indicate that metoprolol slows the sinus rate and decreases AV nodal conduction. The relative beta 1 -selectivity of metoprolol has been confirmed by the following: (1) In normal subjects, metoprolol is unable to reverse the beta 2 -mediated vasodilating effects of epinephrine. This contrasts with the effect of nonselective beta-blockers, which completely reverse the vasodilating effects of epinephrine. (2) In asthmatic patients, metoprolol reduces FEV 1 and FVC significantly less than a nonselective beta-blocker, propranolol, at equivalent beta 1 -receptor blocking doses. Hypertension: The mechanism of the antihypertensive effects of beta-blocking agents has not been elucidated. However, several possible mechanisms have been proposed: (1) competitive antagonism of catecholamines at peripheral (especially cardiac) adrenergic neuron sites, leading to decreased cardiac output; (2) a central effect leading to reduced sympathetic outflow to the periphery; and (3) suppression of renin activity. Angina Pectoris: By blocking catecholamine-induced increases in heart rate, in velocity and extent of myocardial contraction, and in blood pressure, metoprolol reduces the oxygen requirements of the heart at any given level of effort, thus making it useful in the long-term management of angina pectoris. Heart Failure: The precise mechanism for the beneficial effects of beta-blockers in heart failure has not been elucidated.

Metoprolol tartrate tablets are a beta-adrenergic blocker indicated for the treatment of: Hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions. ( 1.1 ) Angina Pectoris. ( 1.2 ) Myocardial Infarction, to reduce the risk of cardiovascular mortality when used in conjunction with intravenous metoprolol therapy in patients with definite or suspected acute myocardial infarction in hemodynamically stable patients. ( 1.3 ) 1.1 Hypertension Metoprolol tartrate tablets are indicated for the treatment of hypertension in adult patients, to lower blood pressure. Lowering blood pressure lowers the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including metoprolol. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than 1 drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit....

Administer once daily with food or after a meal. Titrate at weekly or longer intervals as needed and tolerated. ( 2 ) Hypertension: Recommended starting dosage is 100 mg daily, in single or divided doses. ( 2.1 ) Angina Pectoris: Recommended starting dosage is 100 mg daily, given as two divided doses. ( 2.2 ) Myocardial Infarction: The starting dosage depends upon tolerance of intravenous metoprolol, see full prescribing information. ( 2.3 ) 2.1 Hypertension Individualize the dosage of metoprolol tartrate tablets. Metoprolol tartrate tablets should be taken with or immediately following meals. The usual initial dosage is 100 mg daily in single or divided doses. Adjust dosage at weekly (or longer) intervals until optimum blood pressure reduction is achieved. In general, the maximum effect of any given dosage level will be apparent after 1 week of therapy. The effective dosage range of metoprolol tartrate tablets is 100 mg to 450 mg per day. Dosages above 450 mg per day have not been studied. While once-daily dosing can maintain a reduction in blood pressure throughout the day, lower doses (especially 100 mg) may not maintain a full effect at the end of the 24-hour period. Larger or more frequent daily doses may be required. Measure blood pressure near the end of the dosing interval to determine whether satisfactory control is being maintained throughout the day. 2.2 Angina Pectoris The dosage of metoprolol tartrate tablets should be individualized. Metoprolol tartrate tablets should be taken with or immediately following meals. The usual initial dosage is 100 mg daily, given in two divided doses. Gradually increase the dosage at weekly intervals until optimum clinical response has been obtained or there is a pronounced slowing of the heart rate. The effective dosage range of metoprolol tartrate tablets is 100 to 400 mg per day. Dosages above 400 mg per day have not been studied. If treatment is to be discontinued, reduce the dosage gradually over a period of 1 to 2 weeks [see (5.1) ]. 2.3 Myocardial Infarction See prescribing information of intravenous metoprolol for dosage instructions for intravenous therapy. In patients who tolerate the full intravenous dose, initiate metoprolol tartrate tablets, 50 mg every 6 hours, 15 minutes after the last intravenous dose of metoprolol and continue for 48 hours. In the case of intolerance, reduce dose to 25 mg and administer for 48 hours. Titrate, based on tolerability, to a maintenance dosage of 100 mg twice daily....

The following are described elsewhere in labeling: Worsening angina or myocardial infarction [see (5) ] Worsening heart failure [see (5) ]. Worsening AV block [see (4) ]. ­Most common : tiredness, dizziness, depression, shortness of breath, bradycardia, hypotension, diarrhea, pruritus, rash. ( 6.1 ) To report SUSPECTED , contact Rising Pharma Holdings, Inc. at 1-844-874-7464 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Hypertension and Angina Most adverse effects have been mild and transient. Central Nervous System: Tiredness and dizziness have occurred in about 10% of patients. Depression has been reported in about 5 of 100 patients. Mental confusion and short-term memory loss have been reported. Headache, nightmares, and insomnia have also been reported. Cardiovascular: Shortness of breath and bradycardia have occurred in approximately 3% of patients. Cold extremities; arterial insufficiency, usually of the Raynaud type; palpitations; heart failure exacerbations; peripheral edema; and hypotension have been reported in about 1% of patients. Gangrene in patients with pre-existing severe peripheral circulatory disorders has also been reported. [see (4) and (5.2) ]. Respiratory: Wheezing (bronchospasm) and dyspnea have been reported in about 1% of patients [see (5.3) ] . Rhinitis has also been reported. Gastrointestinal: Diarrhea has occurred in about 5% of patients. Nausea, dry mouth, gastric pain, constipation, flatulence, and heartburn have been reported in about 1% of patients. Vomiting was a common occurrence. Hypersensitive Reactions: Pruritus or rash have occurred in about 5% of patients. Photosensitivity and worsening of psoriasis has been reported. Miscellaneous: Peyronie’s disease, musculoskeletal pain, blurred vision, and tinnitus has been reported. Myocardial Infarction In general, the observed in trials with metoprolol in MI are consistent with the hypertension and angina experience. In a randomized comparison of metoprolol and placebo in the setting of acute MI the following were reported: Metoprolol Placebo Hypotension (systolic BP < 90 mm Hg) 27.4% 23.2% Bradycardia (heart rate < 40 beats/min) 15.9% 6.7% Second- or third-degree heart block 4.7% 4....

Metoprolol tartrate tablets are contraindicated in severe bradycardia, second- or third-degree heart block, cardiogenic shock, systolic blood pressure <100, decompensated heart failure, sick sinus syndrome (unless a permanent pacemaker is in place), and in patients who are hypersensitive to any component of this product. Known hypersensitivity to product components. ( 4 ) Severe bradycardia: Greater than first degree heart block, or sick sinus syndrome without a pacemaker. ( 4 ) Cardiogenic shock or decompensated heart failure. ( 4 )